Summary Low back pain (LBP) is one of the most common reasons for all physician visits in the USA. The financial costs associated with the care of LBP are staggering. The treatments for chronic low back pain (cLBP) are far from satisfactory. Insurance claims data reveal that opioids are the most commonly prescribed class of drug for back pain, and more than half of regular opioid users reported using them for the treatment of back pain. Meanwhile, few new non-opioid and non-addictive pain medications have been developed in nearly five decades; thus, there is an urgent need for the development of new therapies for chronic low back pain. The vagus nerve (VN) consists of a complex network that regulates pain, mood, and the neuro-endocrine- immune axis. Studies suggest that auricular transcutaneous vagus nerve stimulation (tVNS), a non-invasive therapeutic method, can induce antinociception, which may affect peripheral and central nociception, inflammatory responses, autonomic activity, and pain-related behavior. Clinical studies and our pilot study have also shown that tVNS can significantly reduce symptoms of chronic pain and common comorbidities of chronic pain, such as depression and anxiety, thereby endorsing its potential for the treatment of cLBP. This proposal aims to investigate the treatment effect and underlying mechanism of tVNS on chronic low back pain. Patients with chronic low back pain will be randomized to either real or sham tVNS treatment for one month, with a three-month follow up. In addition to clinical outcome measurements, multiple brain imaging modalities, Quantitative Sensory Testing, and blood inflammation markers will be assessed. We believe that this study, if successful, will provide new treatment options for chronic low back pain, reduce the use of opioid analgesics in chronic pain management, and enhance our understanding of the underlying mechanism of tVNS treatment, as well as the pathophysiology and development of chronic pain.